The study shows that in mouse mast cells, the antimicrobial peptide similar to human LL‑37 (called CRAMP) is turned on by the NF‑κB pathway when the cells detect bacterial components, while other signaling routes (MAPKs) don’t matter much. This means that anything that blocks NF‑κB could lower LL‑37 levels and possibly weaken innate immunity, but boosting NF‑κB might raise them.

An important aspect of the innate immune response to pathogens is the production of anti-microbial peptides such as cathelicidin-related antimicrobial peptide (CRAMP), the murine homologue of human cathelicidin LL-37. In this study, mechanisms regulating LPS-induction of CRAMP gene expression in mast cells were investigated. NF-kappaB and MAPK pathways were the focus of investigation. Mouse bone marrow-derived mast cells were grown in culture and stimulated with LPS. MAPKs and NF-kappaB were monitored by immunoblot analysis. ERK, JNK and p38 MAPK were inhibited using siRNAs or a pharmacological inhibitor. Accumulation of the p65 component of NF-kappaB was inhibited by siRNA and NF-kappaB activation was inhibited by overexpression of I kappaB alpha. MEKK2 or MEKK3 were overexpressed by transfection. The effects of all of these treatments on CRAMP gene expression were monitored by RT-PCR. Inhibition of ERK, JNK or p38 MAPK had little discernible effect on LPS-inducible CRAMP gene expression. Overexpression of MEKK2 or MEKK3 likewise had little impact. However, inhibition of the accumulation of p65 NF-kappaB prevented LPS-induced CRAMP mRNA. An important role for NF-kappaB in CRAMP gene expression was confirmed by overexpression of I kappaB alpha, which reduced both basal and induced levels of CRAMP mRNA. NF-kappaB, but not MAPKs, plays an important role in LPS-mediated induction of CRAMP gene in mast cells. Defects which inhibit NF-kappaB activity may increase susceptibility to bacterial and viral pathogens which are sensitive to cathelicidins.